Hamon Y, Broccardo C, Chambenoit O, Luciani M F, Toti F, Chaslin S, Freyssinet J M, Devaux P F, McNeish J, Marguet D, Chimini G
Centre d'Immunologie INSERM-CNRS de Marseille Luminy, Marseille, France.
Nat Cell Biol. 2000 Jul;2(7):399-406. doi: 10.1038/35017029.
ATP-binding-cassette transporter 1 (ABC1) has been implicated in processes related to membrane-lipid turnover. Here, using in vivo loss-of-function and in vitro gain-of-function models, we show that ABC1 promotes Ca2+-induced exposure of phosphatidylserine at the membrane, as determined by a prothrombinase assay, membrane microvesiculation and measurement of transbilayer redistribution of spin-labelled phospholipids. That ABC1 promotes engulfment of dead cells is shown by the impaired ability of ABC1-deficient macrophages to engulf apoptotic preys and by the acquisition of phagocytic behaviour by ABC1 transfectants. Release of membrane phospholipids and cholesterol to apo-AI, the protein core of the cholesterol-shuttling high-density lipoprotein (HDL) particle, is also ABC1-dependent. We propose that both the efficiency of apoptotic-cell engulfment and the efflux of cellular lipids depend on ABC1-induced perturbation of membrane phosphatidylserine turnover. Transient local exposure of anionic phospholipids in the outer membrane leaflet may be sufficient to alter the general properties of the membrane and thus influence discrete physiological functions.
ATP结合盒转运蛋白1（ABC1）与膜脂周转相关过程有关。在此，我们利用体内功能丧失和体外功能获得模型表明，ABC1可促进凝血酶原酶测定、膜微泡形成以及自旋标记磷脂跨膜重分布测量所确定的Ca2+诱导的膜上磷脂酰丝氨酸暴露。ABC1促进死细胞吞噬的证据是，缺乏ABC1的巨噬细胞吞噬凋亡猎物的能力受损，以及ABC1转染细胞获得吞噬行为。膜磷脂和胆固醇向载脂蛋白AI（胆固醇转运高密度脂蛋白（HDL）颗粒的蛋白核心）的释放也依赖于ABC1。我们提出，凋亡细胞吞噬效率和细胞脂质外流均取决于ABC1诱导的膜磷脂酰丝氨酸周转扰动。外膜小叶中阴离子磷脂的短暂局部暴露可能足以改变膜的一般特性，从而影响离散的生理功能。
